Amyotrophic Lateral Sclerosis (ALS) is characterized primarily by progressive loss of motoneurons (MNs). Cranial MN manifestations of ALS, primarily muscle weakness, contribute significantly to patient morbidity and mortality. In this context, the overall objective of this proposed research is to elucidate how cranial MN loss contributes to the deterioration of two important orofacial motor functions, speech and swallowing. ALS-related orofacial weakness causes debilitating changes in communication manifest as dysarthria and ultimately, anarthria,as well as swallowing disorders which contribute directly to aspiration pneumonia and nutritional deficiency. Of particular focus in the present research will be the unequivocal and disproportionate deterioration in the hypoglossal motoneurons with resultant tongue weakness and consequent alteration in speech and swallowing. However, these salient changes in the hypoglossal complex will be evaluated relative to changes in the facial and trigeminal motoneurons. The specific issues to be addressed are how functional deficits of speech and swallowing are influenced by: orofacial (lip, tongue, jaw) weakness, the reduced ability to move these oral structures, loss of orofacial muscle tissue, and associated patterns of denervation and reinnervation. Multiple techniques, including magnetic resonance imaging, instrumental strength measures, X-ray microbeam-based movement, and clinical electromyography will be focused on these issues in a systematic longitudinal investigation in combination with a key set of parallel cross-sectional studies. All studies will include ALS subjects with age, sex and body-weight matched controls. One experimental series will also include a lower motoneuron group (myasthenia gravis) and an upper motoneuron group (cortical stroke). Insights provided on ALS impairments of oral-motor functions will contribute to improved diagnosis, prognosis and management of the very serious cranial motor losses associated with this insidious disease.